Variant 6-44393572-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001253.4(CDC5L):c.438G>A(p.Glu146=) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.0115 in 1,612,410 control chromosomes in the GnomAD database, including 137 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0077 ( 8 hom., cov: 31)

Exomes 𝑓: 0.012 ( 129 hom. )

Consequence

CDC5L
NM_001253.4 splice_region, synonymous

Scores

Splicing: ADA: 0.00006784

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.65

Variant links:

Genes affected

CDC5L (HGNC:1743): (cell division cycle 5 like) The protein encoded by this gene shares a significant similarity with Schizosaccharomyces pombe cdc5 gene product, which is a cell cycle regulator important for G2/M transition. This protein has been demonstrated to act as a positive regulator of cell cycle G2/M progression. It was also found to be an essential component of a non-snRNA spliceosome, which contains at least five additional protein factors and is required for the second catalytic step of pre-mRNA splicing. [provided by RefSeq, Jul 2008]

CDC5L links:

POLR1C (HGNC:):

POLR1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP6

Variant 6-44393572-G-A is Benign according to our data. Variant chr6-44393572-G-A is described in ClinVar as [Benign]. Clinvar id is 2571250.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1178 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CDC5L	NM_001253.4 linkuse as main transcript	c.438G>A	p.Glu146=	splice_region_variant, synonymous_variant	4/16	ENST00000371477.4
POLR1C	NM_001318876.2 linkuse as main transcript	c.946-48318G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDC5L	ENST00000371477.4 linkuse as main transcript	c.438G>A	p.Glu146=	splice_region_variant, synonymous_variant	4/16	1	NM_001253.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00775

AC:

1179

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00265

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.00379

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0126

Gnomad OTH

AF:

0.00670

GnomAD3 exomes

AF:

0.00824

AC:

2060

AN:

250100

Hom.:

AF XY:

0.00847

AC XY:

1146

AN XY:

135256

show subpopulations

Gnomad AFR exome

AF:

0.00247

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00538

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00348

Gnomad FIN exome

AF:

0.00760

Gnomad NFE exome

AF:

0.0135

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.0119

AC:

17312

AN:

1460120

Hom.:

129

Cov.:

AF XY:

0.0116

AC XY:

8441

AN XY:

726398

show subpopulations

Gnomad4 AFR exome

AF:

0.00195

Gnomad4 AMR exome

AF:

0.00313

Gnomad4 ASJ exome

AF:

0.00649

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00771

Gnomad4 NFE exome

AF:

0.0140

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00774

AC:

1178

AN:

152290

Hom.:

Cov.:

AF XY:

0.00729

AC XY:

543

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.00265

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.0126

Gnomad4 OTH

AF:

0.00664

Alfa

AF:

0.0121

Hom.:

Bravo

AF:

0.00730

Asia WGS

AF:

0.00779

AC:

AN:

3478

EpiCase

AF:

0.0128

EpiControl

AF:

0.0135

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2023

CDC5L: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000068

dbscSNV1_RF

Benign

0.020

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over